BISP194: MOLECULAR MECHANISM OF SYNAPTIC PLASTICITY Spring Quarter

Transcription

1 BISP194: MOLECULAR MECHANISM OF SYNAPTIC PLASTICITY Spring Quarter 2011 Instructor: Class Website: Gentry N. Patrick Class Meetings: Tuesday, 11 12:30 pm, YORK 3010 Format: Prospectus: Prerequisites: Texts: Critical highly interactive group discussion of published papers facilitated by small group presenters. We will explore primarily postsynaptic mechanisms of synaptic plasticity. This will include published work which has addressed the importance of glutamate receptor trafficking, postsynaptic scaffold and key signaling molecules, actin cytoskeleton, gene expression, protein synthesis, and protein degradation. Our goal will be to understand current views about the molecular mechanisms of synaptic plasticity and to gain experience in critical thinking about experiments and results. Upper division courses in biochemistry and genetics or their equivalents (required), and a course in neurobiology and structural biology (recommended). None required. For background/introduction: review Chap 48 (pp ) in Biology by Campbell and Reece, 7 th edition, 2005 (Pearson/Benjamin-Cummings), or the equivalent. Assigned articles and review articles will be posted on the website as downloadable PDFs. Reference articles will also be posted on the website as down-loaded PDFs but are not required reading but you are encouraged to read them. Reference sources: Chap 1-11 in Synapses by Cowan, Sudhof, and Stevens, 2001 (Johns Hopskins University Press) Chap 2, 5-15, and 65 in Principles of Neural Science by Kandel, Schwartz, and Jessell, 3 rd edition, 1991 (Elsevier Science Publishing). Exams and grading: Grades will be determined by the quality of student written work and oral presentations, as well as the level of preparedness and participation in all class discussions. Evaluations will be based on performance related to these requirements: 1. Presentations: Oral group presentation of assigned research article. 2. Participation: Involvement in all weekly discussions of

2 research articles. 3. Evaluations: Written evaluations of weekly presentations. 4. Final - Take Home Final due June 7 th by 5 pm Drop off Final at 2222A Pacific Hall Attendance: Office hours: Mandatory (sign in sheet will be utilized) given that participation in class is the primary basis for grade assignment. G.Patrick office hours: Friday 10-11:30 am. 2222A Pacific Hall. gpatrick@ucsd.edu; phone: When sending s: be sure to add BISP194 to subject line or else your s will not be read.

3 Course Schedule: March 29 th : Introduction to Synapses and Synaptic Plasticity Part I Class logistics and group assignment of paper presentations. April 5 th : Introduction to Synapses and Synaptic Plasticity Part II Review Article: Lynch, G. and Baudry, M. (1984) The biochemistry of memory: a new and specific hypothesis Science 224(4653): Review Article: Citri, A and Malenka, RC (2008) Synaptic plasticity: multiple forms, functions, and mechanisms. Neuropsychopharmacology 2008 Jan;33(1): April 12 th : Silent Synapses Review Article: Kerchner GA, Nicoll RA. (2008) Silent synapses and the emergence of a postsynaptic mechanism for LTP Nat Rev Neurosci. Nov;9(11): Article#1: Gomperts, S., et. al. (1998) Postsynaptic silent synapses in single neuron cultures Neuron 21(6): Article #2: Liao et al. (1995) Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature 375: April 19 th : Long term potentiation (LTP) and AMPA receptors

4 Review article: Shepherd JD, Huganir RL. (2007) The cell biology of synaptic plasticity: AMPA receptor trafficking Annu Rev Cell Dev Biol. 2007;23: Article#1: Hayashi, Y., et. al. (2000) Driving AMPA receptors into synapses by LTP and CamKII: requirement for GluR1 and PDZ domain interaction Science 287(5461): Article#2: Lu, W., et. al. (2001) Activation of synaptic NMDA receptors induces membrane insertion of new AMPA Receptors and LTP in cultured hippocampal neurons Neuron 29(1): April 26 th : Long term depression (LTD) and AMPA receptors Article#1: Carroll, R., et. al. (1999) Rapid redistribution of glutamate receptors contributes to long term depression in hippocampal cultures Nature Neuroscience 2(5): Article#2: Lee, HK, et. al. (1998) NMDA induces long term synaptic depression and dephosphorylation of the GluR1 subunit of AMPA receptors in hippocampus Neuron 21(5):

5 May 3 rd : An Important molecules in plasticity Review Article: Kim, E. and Sheng, M. (2004) PDZ domain proteins of synapses Nature Reviews Neuroscience 5(10): Article#1: Miguad, M., et. al. (1998) Enhanced long term potentiation and impaired learning in mice with mutant postsynaptic density 95 protein Nature 396(6710): Article#2: Chen et al., (2000) Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms. Nature 408(6815): May 10 th : AMPA receptor endocytosis Review article: Carroll, R., et. Al (2001) Role of AMPA receptor endocytosis in synaptic plasticity Nature Reviews Neuroscience 2(5): Article#1: Man, HY, et. al. (2000) Regulation of AMPA receptor mediated synaptic transmission by clathrin dependent receptor internalization Neuron 25(3):

6 Article#2: Hsieh, H., et. al. (2006) AMPAR removal underlies Aβ-induced synaptic depression and dendritic spine loss Neuron 52(5): May 17 th : NO CLASS TAKE HOME READING/ASSIGNMENT Greer et al., (2010) The Angelman Syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell. Mar 5;140(5): ANSWER FOLLOWING QUESTIONS (1 page typed max - Due May 24 th ): 1. What is the take-home message of the paper? 2. Describe one or two key experiments that substantiates the author s hypothesis/conclusions. 3. Is the hypothesis/take home message put forward by the authors substantiated by the findings presented in the paper? Why or Why not? May 24 th : Diffusion of AMPA receptors in the plasma membrane Review article: Choquet, D. and Triller, A. (2003) The role of receptor diffusion in the organization of the postsynaptic membrane Nature Reviews Neuroscience 4(4): Article#1: Borgdorff A. and Choquet, D. (2002) Regulation of AMPA receptor lateral movements Nature 417(6889):

7 Article#2: Adesnik et al. (2005) Photoinactivation of native AMPA receptors reveals their real-time trafficking. Neuron Dec 22;48(6): May 31 th : Actin cytoskeleton and plasticity Review article: Luo, L. (2002) Actin cytoskeleton regulation in neuronal morphogenesis and structural plasticity Annual Reviews Cell Developmental Biology 18:601-35] Article#1: Fisher et al. (2000) Glutamate receptors regulate actinbased plasticity in dendritic spines. Nature Neuroscience 3(9): Protein synthesis and protein degradation in synaptic plasticity Article#1: Aakalu et al. (2001) Dynamic visualization of local protein synthesis in hippocampal neurons. Neuron 30(2): June 7 th : Final - Take Home Final due June 7 th by 5 pm Drop off Final at 2222A Pacific Hall